The effect of intravenous administration of morphine and related opiates will be determined on heart rate, blood pressure, respiration rate (and blood pH, pCO2, pO2) and rectal temperature in conscious rabbits previously prepared with cannulae in either the ear artery or in lateral ventricle and cisterna magna. Morphine will then be given by continuous infusion over a period of several hours until acute tolerance to some or all the above effects of mophine develop. The effect of acute and chronic morphine administration on spontaneous acetylcholine release into fluid perfusing through permanently implanted intraventricular and intracisternal cannulae will be determined and related to the cardiovascular and respiratory effect. Studies will also be made of the effects of intracisternal and intraventricular injection of cholinergic agonists on blood pressure, heart rate and respiration. It is intended to see whether acute tolerance to the effects of opiates is related to hypersensitivity of target cells in the vagal, vasomotor and respiratory centers to cholinergic agonists.